The noradrenalin and serotonin re-uptake inhibitor venlafaxine has an analgesic eŠect that is independent of its antidepressant activity; however, the mechanism of this eŠect remains to be elucidated. This study was performed to investigate the possible roles of the opioidergic system and nitric oxide (NO) pathway in the analgesic eŠect of venlafaxine. Eighty Wistar rats of both sexes were allocated to 10 groups. The hot plate test was used to assess the antinociceptive/ analgesic eŠect. The temperature of the hot plate was adjusted to 52.5±1°C, the cut oŠ period was set to be 50 sec; licking of the hind paw was used as a sign of pain perception. Venlafaxine alone (25 mg/kg) showed marked analgesic activity (p＜0.05). N-v-nitro L-arginine (L-NOARG) alone (20 mg/kg) and naloxone alone (2 mg/kg and 4 mg/kg) showed no analgesic activity (p＞0.05). Coadministration of low-dose naloxone (2 mg/kg) and both doses of L-NOARG (20 and 40 mg/kg) with venlafaxine (25 mg/kg) did not modify the analgesic eŠect but high-dose naloxone (4 mg/kg) decreased it signiˆcantly (p＜0.05). In conclusion, these results suggest that the opioidergic system but not the NO pathway has a role in the analgesic eŠect of venlafaxine.

Abstract. The aim of this study was to investigate the modulatory role of nitric oxide (NO) in the electrical field stimulation (EFS)-induced contractions of isolated sphincter of Oddi (SO) and gallbladder strips from guinea pigs. EFS was used to activate the intrinsic nerves in SO and gallbladder strips. EFS produced frequency-dependent biphasic contractile responses in the SO strips. A smaller contraction, "on response", occurred during EFS, which was followed by a bigger contraction, "off response". Both responses were completely and irreversibly abolished by tetrodotoxin (TTX) (10 −6 M). Atropine (10 −6 M) inhibited the "on response", but not the "off response". EFS produced frequency-dependent monophasic contractile responses in gallbladder strips, which were completely and irreversibly abolished by TTX (10 −6 M) and atropine (10 −6 M). A nitric oxide synthase (NOS) inhibitor, N G -nitro-L-arginine (10 −4 M and 3 × 10 −4 M, in SO and gallbladder strips, respectively), significantly increased all EFS-induced contractions of SO and gallbladder strips. L-Arginine, but not D-arginine reversed the effect induced by the NOS inhibitor, at all frequencies, in both strips. These results suggested that NO released from nitrergic nerve endings might play a regulatory role in the cholinergic neurotransmission of guinea pig SO and gallbladder strips. The "off response" in the SO preparations might be a rebound increase that was modulated by the nonadrenergic, noncholinergic inhibitory mediator NO.

In this study, the effects of 2 volatile anesthetics, desflurane and sevoflurane, on oxytocin-induced contractions of isolated myometrium in pregnant and nonpregnant rats were compared. Twenty pregnant and 20 nonpregnant Wistar albino rats were studied at 19 to 20 days' gestation (term, 22 days). A total of 40 myometrial strips were obtained from pregnant and nonpregnant rats, and each of these was randomly assigned to 1 of 4 groups (n=10, each group). After spontaneous myometrial contractions were induced in the De Jalon solution, the effects of 0.5, 1, and 2 minimum alveolar anesthetic concentrations (MAC) of desflurane or sevoflurane, in the absence and presence of oxytocin (2 x 10(-9) M), were investigated. Oxytocin significantly increased the amplitude and duration of spontaneous contractions in longitudinal myometrial strips (P<.05), but not the frequency. Both agents (except for 0.5 MAC in the nonpregnant group) inhibited the duration, amplitude, and frequency of induced contractions in a dose-dependent manner. The inhibitory potencies of desflurane and sevoflurane were similar. It was found that isolated strips of pregnant rat myometrium were more sensitive to the inhibitory effects of both agents than were the nonpregnant rat myometrial strips.

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